In vivo analysis of molecular mechanism of lymphocyte migration in Peyer's patch

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Gut associated lymphoid tissue (GALT) plays an important role for intestinal mucosal defense against dietary and bacterial antigens. In this study, we have established an observatory system of lymphocyte migration in rat Peyer's patches using intravital fluorescence microscopy. Fluorescence labeled lymphocytes adhered to the postcapillary venules (PCV) of Peyer's patches after transient rolling along venular walls. Lymphocytes sticking to the venules increased in number at 10-20 minutes, with preferential adherence of CD4+ cells to venules of 25-50 mum and adherence of B cells to the venules of a wider size range. In this sticking process, adhesion molecules, alpha4-intgerin, L-selectin and CD18/ICAM-1 are shown to be involved. Especially we demonstrated that alpha4-integrin molecule plays a critical role in the early stages of T lymphocyte migration in Peyer's patches. After 30 min, lymphocytes started to extravasate from PCV moved into the interstitium. B cells migrated from venules more quickly than CD4+ cells. Subsequently T lymphocytes preferentially appeared in parafollicular microlymphatics, while few B cells were transported to lymphatics. We also found that alpha4-integrin plays a significant role in the process of transendothelial migration of T lymphocytes in PCV of Peyer's patches. Fat absorption significantly enhanced the rolling and sticking of T cells and subsequent migration into microlymphatics. On the other hand, vasoactive intestinal peptide (VIP) significantly inhibited the transendothelial migration and lymphatic transport without affecting lymphocyte adherence to PCV.By this study, we were able to demonstrate the sequential migration process of lymphocye subpopulations and obtained informations about their regulatory mechanisms.